I joined the gastroenterology training program at the Brigham and Women's Hospital in July, 1977 and since 1980 have been a member of the junior faculty. I have been studying how selected viruses interact with the intestinal mucosa. As a research fellow, I characterized susceptibility to infection in an important animal model for rotavirus infection, Epizootic Diarrhea of Infant Mice. More recently I have determined that reovirus, a virus that produces systemic infection in mice, penetrates the gastrointestinal mucosa through the M cell, a distinctive cell of the follicular epithelium which has been shown to transport several other macromolecules. Moreover, the viral hemagglutinin of reovirus (outer capsid protein Omega 1) determines how the virus interacts with intestinal epithelial cells and how the virus disseminates from Peyer's patches. The current studies proposed are important extensions of this previous work. I will determine what factors influence reovirus penetration of the gastrointestinal tract. Specifically, using ileal closed loops, I will compare reovirus interaction with proximal Peyer's patches to that with distal Peyer's patches, the influence of passive and active immunity on reovirus penetration of and dissemination from the gastrointestinal tract, and the effect of various hapten sugars on reovirus type 1 and type 3 adherence to epithelial cells. Using immunomicroscopic techniques, I will also examine lectin binding to the surface glycoconjugates of M cells and absorptive cells, determine the distribution of histocompatibility associated antigens on the apical surface of the absorptive and M cells on Peyer's patches, and characterize the distribution of IgA on the apical surface and within the cytoplasm of intestinal M cells.